PROJECT SUMMARY/ABSTRACT The recent emergence of the epitranscriptomics field has opened the possibility to understand and manipulate a previously underappreciated regulatory layer involved in biological processes. In particular, our research focuses on m6A as a candidate of interest given that it is the most prevalent RNA modification in the nervous system that controls multiple aspects of RNA metabolism. We have previously shown the critical roles of m6A regulation in axonal plasticity and synaptic activity. This proposal extends our research scope and focuses on how the m6A epitranscriptome responds to environmental perturbation using innovative methods for the identification of biomarkers and molecular pathways linked to adverse outcomes. We will use system-wide approaches to address the following questions: (i) What is the mechanism to remodel the m6A epitranscriptome upon toxicant exposure, (ii) How do the dynamics of m6A reshape the transcriptome? (iii) What are the characteristics of mis-localized RNA that are associated with disease state and risk? We expect that our proposed study will significantly advance our understanding of how epitranscriptomic regulatory processes constitute key pathogenic mechanisms following environmental challenges. Data gained from our systematic profiling and functional validation may offer new opportunities for developing diagnostics and/or biomarkers to facilitate the development of more effective prevention and treatment strategies for these diseases.